Management’s Discussion and Analysis Year Ended December 31, 2009

Management’s Discussion and Analysis
Year Ended December 31, 2009
DATE OF REPORT: March 29, 2010
CORPORATE OFFICE:
Suite 1210, 885 West Georgia Street
Vancouver, B.C. Canada
V6C 3E8
SYMBOL: PRX (Toronto Stock Exchange - TSX)
CONTACT:
John Parkinson, Chief Financial Officer
Email: [email protected]
1
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
MANAGEMENT’S DISCUSSION AND ANALYSIS
The following management’s discussion and analysis (“MD&A”) has been prepared as of March
29, 2010 and should be read in conjunction with our audited financial statements for the year
ended December 31, 2009 and the Company’s Annual Information Form, dated March 29, 2010
(collectively known as the “Financial Statements”). All the financial information has been
prepared in accordance with Canadian generally accepted accounting principles (“Canadian
GAAP”) and all dollar amounts are expressed in Canadian dollars unless otherwise noted.
Additional information relating to Protox Therapeutics Inc., including the Company’s Financial
Statements, can be found on SEDAR at www.sedar.com and on our website at
www.protoxtherapeutics.com.
ABOUT FORWARD-LOOKING STATEMENTS
This document contains forward-looking statements, which reflect our current expectations
regarding future events. Forward-looking statements may include such words as “plans”,
“expects”, “estimates”, “forecasts”, “intends”, “anticipates”, “believes” or “continues” or
variations of such words and phrases or statements that certain actions, events or results “may”,
“could”, “would”, “might” or “will” be taken, occur or be achieved. With respect to forwardlooking statements and information included herein, we have made numerous assumptions
including among other things, assumptions about our future financing requirements and our
ability to meet our obligations, our ability to meet regulatory requirements, the anticipated market
for our products and our ability to achieve our goals. Even though our management believes that
the assumptions made and the expectations represented by such statements or information are
reasonable, there can be no assurance that the forward-looking statements will prove to be
accurate. By their nature, forward-looking statements and information are based on assumptions
and involve known and unknown risks, uncertainties and other factors, many of which are beyond
the Company’s control that may cause our actual results, events or developments to differ
materially from those that are expressed or implied by such forward-looking information. Such
risks, uncertainties and other factors include, among other things, the following: negative results
from our clinical studies; drug product supply for our clinical trials; inability to fund our
development programs; unexpected delays in drug discovery, clinical development and
manufacturing; program delays due to reliance on third-party service providers; raw material and
operating costs; changes in government regulation; fluctuations in demand and supply for our
products; industry production levels; general economic and business conditions; our ability to
execute our business plan; and those additional risks set forth under the heading "Risk Factors" in
our Annual Information Form for our financial year ending December 31, 2009. Should one or
more of these risks or uncertainties materialize, or should assumptions underlying the forwardlooking statements or information prove incorrect, actual results may vary materially from those
described herein as intended, planned, anticipated, believed, estimated, expected or continued.
Accordingly, readers should not place undue reliance on forward-looking statements or
information. We undertake no obligation to reissue or update forward-looking statements or
information as a result of new information or events after the date hereof except as may be
required by law. All forward-looking statements and information made in this document are
qualified by this cautionary statement pursuant to the “safe harbour” provisions of applicable
securities legislation.
2
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
COMPANY OVERVIEW
Protox Therapeutics Inc. (the “Company” or “Protox”) is a biopharmaceutical company focused
on the research, development and commercialization of novel receptor targeted therapeutic fusion
proteins. These fusion proteins are designed to specifically deliver potent payloads to targeted
tissues or cells to either cause cell death or promote survival without the side-effects normally
associated with conventional therapeutics.
Protox is advancing a pipeline of receptor targeted therapeutic fusion proteins based on three
complementary technology platforms: PORxin™, INxin™ and HUMxin™. The payloads used to
generate our lead compounds are derived from genetically engineered bacterial toxins or fully
human Bcl-2 family of proteins. Our current focus is on the PORxin platform and our lead
candidate, PRX302, has now completed three clinical trials for the treatment of benign prostatic
hyperplasia (“BPH”, commonly known as enlarged prostate) as well as localized prostate cancer.
The INxin candidate, PRX321 has received approval from the U.S. Food and Drug
Administration (“FDA”) for a Phase 2b (pre-pivotal) clinical trial for the treatment of recurrent
glioblastoma multiforme (“GBM”) - the most lethal form of brain cancer. Advancement of the
INxin program will occur once partners or collaborators have been secured to fund further
development activities. The HUMxin platform is in pre-clinical development and will be
advanced once the Company is successful in securing non-dilutive research grants.
The Company continues to work in partnership with co-inventors of the PORxin, INxin and
HUMxin platforms as well as experts and key opinion leaders, or KOLs, in the field in order to
guide the Company in the successful development of our lead candidates as well as strengthen our
product pipeline.
ACHIEVEMENTS & HIGHLIGHTS
The following are the achievements and highlights since 1st January, 2009:
•
In December, 2009, the Company completed its multi-centre, double-blinded placebo
controlled Phase 2b study of PRX302 (study name: TRIUMPH) in patients with moderate to
severe benign prostatic hyperplasia. Positive top-line results from the study were released on
January 11, 2010 indicated that the TRIUMPH study achieved its primary clinical endpoint of
a statistically significant improvement in International Prostate Symptom Score for patients
treated with PRX302 versus subjects receiving placebo.
•
The Company announced positive 12 month data from our open-label Phase 2 study of
PRX302 in males with moderate to severe benign prostatic hyperplasia. The study results
indicated that those patients who received an optimal dose of PRX302 continued to
demonstrate significant symptomatic relief at 12 months following a single treatment. The
results from this study demonstrate the durable impact that this novel therapeutic has on
potentially improving the quality of life of patients suffering with BPH.
•
Data from the Phase 2 clinical study of PRX302 in patients with moderate to severe benign
prostatic hyperplasia was presented at the 2009 Annual Meeting of the American Urological
Association, the world’s largest gathering of urology professionals.
•
In May 2009, the Company closed a brokered private placement raising net proceeds of $2.0
million from the issuance of 8,554,004 common shares. Proceeds included approximately
$800,000 from the exercise of an over-allotment option by the agent.
3
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
•
On March 16th 2010, the Company closed a brokered private placement raising net proceeds
of $4.8 million from the issuance of 11,285,388 units at a price of $0.45 per unit. Each Unit
is comprised of one common share of Protox and one-half of a common share purchase
warrant. Each whole warrant entitles the holder to purchase one common share of Protox at a
price of $0.65 for a five year period from closing date subject to an acceleration of the expiry
date in certain circumstances.
•
An allowance was obtained in Japan by the Japan Patent Office for the Company’s
composition patent of PRX302 and its use in prostate cancer. In addition, an allowance in
China was obtained for the Company’s patent covering composition of PRX302 and its use in
prostate cancer. •
The Company and/ or its collaborators published or presented 10 papers in various peer
reviewed journals and international conferences based on the Company’s PORxin, INxin and
HUMxin platforms. •
Dr. Alex Giaquinto was appointed to the Board of Directors in June 2009. Dr. Giaquinto is a
35 year veteran of the pharmaceutical industry during which time he held a number of senior
regulatory affairs positions with Schering-Plough.
•
The Company appointed Mr. John Parkinson as Chief Financial Officer in March 2009.
Previously he was Vice President, Finance at Aspreva Pharmaceuticals and prior to that he
worked with KPMG for 10 years.
RESEARCH & DEVELOPMENT UPDATE
PORxin Platform
Placebo controlled BPH Study:
During 2009, the Company continued to advance its program for the treatment of benign prostatic
hyperplasia. The Company’s third clinical trial of PRX302 in BPH - a multi-centre, double
blinded, placebo controlled Phase 2b study (study name: TRIUMPH) in males with moderate to
severe BPH – was initiated and completed during the year, with top level results released on
January 11, 2010.
The study achieved its primary clinical endpoint of a statistically significant improvement in
International Prostate Symptom Score (IPSS) for patients treated with PRX302 versus subjects
receiving placebo. IPSS is a validated accepted clinical end-point used to assess the treatment
benefit in BPH clinical studies. The IPSS index is measured on a 0-35 scale with 0 defined as
having no problems and 35 defined as the high end of severe symptoms.
Enrolment criteria included baseline IPSS scores greater than or equal to 15, a maximum urinary
flow rate (Qmax) of less than 12 milliliters per second and prostate volume between 30 and 100
milliliters. Each subject was treated with either PRX302 (3 μg/mL) or placebo at a volume
equivalent to 20 percent of the total prostate volume via a single ultrasound guided injection into
each lobe of the prostate.
The trial’s primary clinical endpoint of the study was to determine the efficacy of PRX302, as
demonstrated at 90 days post-treatment, by a statistically significant improvement in IPSS from
baseline when compared to placebo.
4
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
Of the 73 per protocol efficacy evaluable subjects, 52 received PRX302 and 21 received placebo.
The PRX302 arm showed an average IPSS improvement at 90 days of 9.1 (± 5.9) points versus an
average IPSS improvement of 5.8 (± 5.4) points for the placebo arm, a statistically significant
improvement of 3.3 points (p=0.0238, ANCOVA). Baseline average IPSS for the PRX302 and
placebo groups were 23.5 and 22.9 points, respectively.
A sub-group analysis was performed for subjects with severe BPH (baseline IPSS>22, n=40).
Results of this sub-group analysis showed that those treated with PRX302 had an average IPSS
improvement at 90 days from baseline of 10.8 (± 6.0) versus an improvement of 5.8 (± 6.2) for
those receiving placebo for an overall 5.0 point improvement over placebo.
No significant safety issues were identified in this study. There were no drug related serious
adverse events or Grade 3 or greater adverse events reported in the study. PRX302 related
adverse events were mild to moderate, transient in nature (resolved within days) and localized to
the urinary tract. In addition, no sexual dysfunction was reported in any of the subjects.
A total of 92 subjects were enrolled on a 2-to-1 basis (treatment to placebo) and randomized
based on their baseline IPSS and prostate size. At 90 days, the number of per protocol efficacy
evaluable subjects was 21 (mean age of 64.5 years) of the 31 that were dosed at baseline in the
placebo arm and 52 (mean age of 63.7 years) of the 61 dosed at baseline in the PRX302 arm. The
decrease in efficacy evaluable subjects was due to protocol violations, medical interventions, or
patient withdrawal and included three subjects that needed surgery to treat BPH (all from the
placebo arm).
Detailed results from this clinical trial will be presented by Professor Mostafa Elhilali, the Chief
Co-Principal Investigator of the study, during a podium session at the Annual Meeting of the
American Urological Association to be held in San Francisco, May 29 – June 3, 2010.
The Chief Co-Principal investigators for the TRIUMPH study were Dr Mostafa M. Elhilali, OC,
M.D., Ph.D, Stephen Jarislowsky Chair in Urology at McGill University and Dr. Peter
Pommerville, M.D., Director of Research at Can-Med Clinical Research Centre in Victoria, B.C.
The study was conducted at 9 sites across Canada.
Open label BPH study:
During the third quarter of 2009, the Company announced positive 12 month data from its openlabel Phase 2 study of PRX302 in males with moderate to severe benign prostatic hyperplasia.
The study results indicate that those patients who received an optimal dose of PRX302 continued
to demonstrate significant symptomatic relief at 12 months following a single treatment. A
twelve point improvement in the International Prostate Symptom Score was observed in this
patient group after one year following a single treatment, almost double that seen with oral
therapies and comparable to many surgical procedures. The results demonstrate the durable
impact that this novel therapeutic has on potentially improving the quality of life of patients
suffering with BPH and demonstrates the ability of PRX302 to improve lower urinary tract
symptoms (LUTS) while maintaining a good safety profile.
In this Phase 2 open-label volume optimization study, 13 of the 18 patients received the optimum
PRX302 dosing of > 1mL per deposit. A total of 11 of the 13 patients were evaluable at 12months and continued to show a statistically significant and sustained improvement in IPSS of
12.1 points (p= 0.0003) representing a 55% improvement when compared to baseline. In addition
5
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
to IPSS, Quality of Life (QoL) scores improved significantly by an average of 3.18 points or 67%
(p < 0.0001) at 12 months post-treatment. Furthermore, prostate volume at 12 months posttreatment decreased significantly by 29% (p=0.02). Finally, the average maximum urine flow rate
(Qmax) increased from 10.7mL/sec at screening to 15.2 mL/sec at 12 months for a 42%
improvement in patients receiving the optimum dose.
No safety issues were identified in this study, as increasing volumes of PRX302 were seen to be
well tolerated. No PRX302 related serious adverse events or Grade 3 or greater adverse events
have been reported to date. The PRX302 related adverse events were mild to moderate, transient
in nature (resolved within days) and localized to the urinary tract. In addition, no sexual
dysfunction has been reported in any of the subjects dosed to date.
This was a single-arm, open-label, multi-centre, Phase 2 study in which increasing volumes of
PRX302, at a fixed concentration of 3 μg/mL, was administered into the prostates of men with
moderate to severe BPH. Three cohorts of six subjects each received PRX302 at volumes
equivalent to 10%, 20% or 30% of prostate volume. The intended volume for each subject was
administered via a single injection consisting of three deposits into each lobe of the prostate under
ultrasound guidance. Therapeutic activity was measured by the change in IPSS when compared to
screening. In addition, changes in QoL scores and prostate volume, Qmax were also monitored. A
total of 18 patients who were refractory, intolerant or unwilling to use alpha-blockers were
enrolled in this study. Patient parameters at screening were as follows: age - 66.1 years (range:
49-80); prostate size - 49.2 cc (range: 30.0-74.0 cc); IPSS - 20.2 (range: 13-30); QoL - 4.5 (range:
3-6).
Detailed 12-month results from this Phase 2 open-label clinical trial were presented by Dr.
Pommerville at the 30th World Congress of the Societe Internationale d'Urologie held in
Shanghai in November 2009.
INxin Platform
Based on encouraging Phase 1 and 2a study results of PRX321, the Company had anticipated
initiating in 2009 a multi-centre Phase 2b (pre-pivotal) clinical trial in patients with recurrent
malignant glioblastoma multiforme (“GBM”). Although the preparations for the study were
completed, including FDA approval to proceed, patient enrolment was deferred until a suitable
partner is identified to fund further clinical development of this program. The deferral of
enrolment of this GBM study has enabled the Company to conserve cash and allocate resources to
our lead PRX302 BPH clinical program.
The Company continues to support a collaborative research program with the FDA under the
terms of a collaborative research and development agreement (CRADA) to further investigate IL4R-directed agents such as PRX321 on various human tumours, including bladder and thyroid
cancers.
In addition, the Company is currently collaborating with Dr. Bhaumik Patel, MD, PhD, on a
research program evaluating PRX321 for colon, pancreatic and gastric cancer stem cells. This
collaboration is being performed under a CRADA with the U.S. Department of Veterans Affairs
and Metropolitan Detroit Research and Education Foundation.
An investigator-initiated collaboration is also underway with Dr. Robert Cameron, MD, at UCLA
on evaluating PRX321 for treatment of malignant mesothelioma.
6
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
HUMxin Platform
HUMxin, a next-generation platform technology in-licensed in 2007, is being developed in
collaboration with the U.S. National Institutes of Health with an objective to develop novel
receptor targeted fusion proteins, using the fully human Bcl-2 family of proteins as payloads, in
order to accelerate or prevent apoptosis (programmed cell death). Further advancement of this
program will take place once the Company has secured research grants to fund the ongoing costs.
In 2009, the Company continued collaborative research with the University of Alabama at
Birmingham under the direction of Dr. Candace Floyd. This collaboration focused on three
HUMxin compounds (PRX341, PRX342 and PRX343) and generated impressive preliminary
results. All three compounds were shown to have a protective effect in animal models of spinal
cord injury. The data from a large placebo-controlled double blinded study demonstrated
significant functional improvement post-spinal cord injury in the rat as determined using two
different types of injury assessments. In addition, the HUMxin compounds were shown to induce
significant increases in neuronal survival, double the percentage of spared white matter,
substantially reduce apoptotic cell death and promote significant recovery of lower urinary tract
function. Subsequent studies in a guinea pig model of spinal cord injury also showed significant
neural survival. Thus, based on these preliminary studies, HUMxin compounds are able to inhibit
neuron apoptosis, thereby promoting the recovery of injured neurons and potentially delaying the
progression of neurodegenerative diseases.
Publications - Clinical, Pre-Clinical and Collaborative Research Programs
During 2009, the following papers were published in peer reviewed journals or presented at
various international conferences:
Title
Senior Author
Publication or
Conference
Convection-enhanced drug delivery of
interleukin-4 Pseudomonas exotoxin
(PRX321): increased distribution and magnetic
resonance monitoring
Dr. Zvi Ram
The Journal of
Pharmacology and
Experimental
Therapeutics, Online
issue dated, May 28,
2009
Long-term safety of combined intracerebral
delivery of free gadolinium and targeted
chemotherapeutic agent PRX321
Dr. John Sampson
Neurological Research,
Online issue dated
December 21, 2009
7
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
Title
Senior Author
Publication or
Conference
A review of studies on targeting interleukin-4
receptor for central nervous system
malignancy
Dr BH Joshi
Current Molecular
Medicine, August 2009,
Volume 9(6), p.732-739
Identification and characterization of
interleukin-4 receptor alpha chain human
anaplastic thyroid carcinoma and targeting of
IL-4 receptor for therapy
Dr. Raj Puri
24th Annual Meeting of
the International Society
for Biological Therapy
for Cancer, October 2931, 2009, Washington,
DC
In vivo overexpression of Interleukin 4
Receptor α (IL-4Rα) in a mouse model of
human bladder carcinoma sensitizes tumors to
recombinant chimeric immunotoxin consisting
of Interleukin 4 and Pseudomonas exotoxin
Dr. Raj Puri
24th Annual Meeting of
the International Society
for Biological Therapy
for Cancer, October 2931, 2009, Washington,
DC
A PSA-activated protoxin (PRX302)
administered transperineally to men with BPH
is well tolerated and induces reduction in
prostate volume and symptomatic relief
Dr. Peter
Pommerville
Annual Meeting of the
American Urological
Association, 25th – 30th
April, 2009 Chicago,
USA
PRX302, a PSA-Activated Protoxin, is Well
Tolerated and Induces Symptomatic Relief and
Prostate Volume Reduction when
Administered Transperineally to Men with
BPH
Dr. Peter
Pommerville
64th Annual Meeting of
the Canadian Urological
Association, June 28 –
July 1, 2009, Toronto,
Canada
A PSA-activated protoxin (PRX302)
administered transperineally to men with
symptomatic benign hyperplasia is well
tolerated and exhibits signs of activity
Dr. Peter
Pommerville
Annual Congress of the
European Association
of Urology, 17th – 21st
March, 2009,
Stockholm, Sweden
8
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
Title
Senior Author
Publication or
Conference
PRX302 is a transperineally administered,
PSA-activated protoxin that produces
symptomatic relief in men with moderate to
severe BPH
Dr Peter
Pommerville
30th Congress of Société
Internationale
d'Urologie, November 1
-5, 2009, Shanghai,
China
PRX303 is an IL-2 Proaerolysin Fusion
Protein Toxin that Selectively Targets and
Kills FOXP3 Regulatory T Cells: Potential
Role as a Vaccine Adjuvant
Dr. Sam Denmeade
2009 Whistler Keystone
Symposium: targeted
Cancer Therapies,
March 27 – April 1,
2009, Whistler, BC
Bcl fusion proteins: Therapeutic implications
after spinal cord injury
Dr. Candace Floyd
2009 Joint Symposium
of the International and
National Neurotrauma
Societies, September 711, 2009, Santa
Barbara, California
INTELLECTUAL PROPERTY
We regard our patent and other proprietary technology rights as one of the foundation blocks
upon which we continue to build a successful biopharmaceutical development company and,
therefore, we file and prosecute patent applications to protect our proprietary discoveries.
During 2009, we supplemented our patent portfolio with allowances in Japan and China for the
Company’s patent covering composition of PRX302 and its use in prostate cancer.
Patents and patent applications covering the PORxin technology licensed or owned by the
Company are currently being prosecuted under the following five patent families:
i)
Proaerolysin Containing Protease Activation Sequences and Methods of Use for
Treatment of Prostate Cancer;
ii) Method of Treating or Preventing Benign Prostatic Hyperplasia Using Modified PoreForming Proteins;
iii) Modified Pore-Forming Protein Toxins and Use Thereof;
iv) Modified Protein Toxins and Use Thereof for Treating Disease; and
v) Method and Composition for Treating Prostatitis.
Eight issued patents in various territories, including the U.S., as well as Japan, Australia, India,
China and South Africa, cover composition of matter and method of use for the PRX302 drug
candidate and the PORxin technology. Several other patent applications are pending
internationally.
9
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
The INxin technology licensed by the Company is covered by issued patents and patent
applications under the following six patent families:
i)
Fusion Proteins Comprising Circularly Permuted Ligands;
ii) Circularly Permuted Ligands and Circularly Permuted Chimeric Molecules;
iii) Convection-Enhanced Drug Delivery;
iv) Method for Convection-Enhanced Delivery of Therapeutic Agents;
v) Targeted Cargo Protein Combination Therapy; and
vi) Treating Cancer Stem Cells Using Targeted Cargo Proteins.
Seven issued patents in the U.S., Europe, Canada and Australia cover the composition of matter
and method of use of the PRX321 drug candidate and the INxin technology. Several other patent
applications have been filed by the Company and are pending. As PRX321 has been granted
Orphan Drug Status by the FDA and EMEA, the market exclusivity of PRX321 will be extended
by seven and ten years, respectively, if the drug candidate is successfully approved. Under the
terms of the FDA CRADA, Protox has an exclusive option to license any future inventions
developed under this INxin research program.
The HUMxin technology licensed by the Company is covered by worldwide patent applications
under the following patent family: methods and compositions for Inhibiting Cell Death or
Enhancing Cell Proliferation.
In relation to the HUMxin technology and intellectual property being developed under the
NINDS CRADA, Protox has an exclusive option to license any future inventions developed under
this HUMxin research program.
SELECTED FINANCIAL INFORMATION
Summary annual results for the three most recently completed years (audited):
Years ended December 31:
Net loss (in thousands)
Loss per share
Total assets (in thousands)
2009
2008
$ (7,944.5)
(0.10)
2,778.1
$ (8,919.1)
(0.12)
8,458.1
2007
$ (7,446.1)
(0.13)
12,913.7
The Company has not earned any revenue in any of its previous fiscal years, other than income from
interest earned on the Company's investment balances. We anticipate that this will continue into the
foreseeable future.
Expenses, in particular research and development costs, are influenced by a number of factors
including the scope of clinical development and research programs pursued; the type and size of
clinical trials undertaken; the number of clinical trials that are active during a particular period of
time; the rate of patient enrollment; and are ultimately a function of decisions made to continue
the development and testing of a product candidate based on supporting safety and efficacy from
clinical trial results. Consequently, expenses vary from period to period. General and
administrative expenses will be dependent on the personnel and infrastructure required to support
the corporate, clinical and business development objectives and initiatives of the Company.
10
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
RESULTS OF OPERATIONS
Year ended December 31, 2009 compared to the year ended December 31, 2008:
The net and comprehensive loss reported for the year ended December 31, 2009 (“2009-FY”)
totaled $7.9 million or $0.10 per share compared to $8.9 million or $0.12 per share for the year
ended December 31, 2008 (“2008-FY”).
Total expenses for the year ended December 31, 2009 decreased by $1.0 million over the
preceding year primarily due to the Company’s efforts to focus its resources on the lead program,
PRX302 for the treatment of BPH. Activities in the Company’s other programs, including its
INxin and HUMxin platforms, were limited and clinical activities related to them have been
deferred until grant or other sources of financing has been secured. Efforts to reduce costs across
all areas of the Company, including general and administration, also were successful in reducing
the net loss compared to the prior year.
Research and Development Costs
Research and development (“R&D”) costs for the 2009-FY period totaled $5.5 million representing a
$681,000 (11%) decrease from $6.2 million incurred during the 2008-FY comparative period,
reflecting the effects of the consolidation of our research and development programs to focus on
the lead BPH program.
Clinical and regulatory costs incurred in 2009 for our PRX302 clinical programs for the treatment
of BPH and prostate cancer as well as basic maintenance activities associated with our reduced
PRX321 program totaled $4.8 million compared to $4.9 million for 2008. The decrease is driven
by the significant drop in our non-BPH programs from the previous year with the narrowing of
the Company’s focus to the core BPH program, offset by the high costs of the TRIUMPH study
which was initiated and completed during 2009.
Research and development costs are expected to decrease in 2010 as our overall clinical activity
will decline as we concentrate on our efforts on regulatory activities associated with preparing our
BPH program for a phase 3 study and to be partner-ready.
General and Administrative Costs
2009-FY general and administrative (“G&A”) costs of $2.1 million decreased $186,000 (8%) from
the $2.3 million incurred during 2008-FY. General and administrative costs will generally vary from
period to period depending on the specific business development, market research and shareholder
relations initiatives undertaken and related travel required at such time to support the Company’s
corporate objectives. The general and administrative costs incurred in 2009 reflect the shift in efforts
implemented in the first quarter of 2009 to consolidate and focus operations on our lead clinical BPH
program and the Company’s efforts to stabilize and reduce overhead costs in the future. This
reduction in G&A costs will provide the Company with more resources to focus on the
completion of its clinical programs. General and administrative costs are expected to continue to
decline in 2010.
11
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
Stock Based Compensation
Stock based compensation costs of $339,000 for 2009-FY decreased $77,000 (19%) from the
$416,000 incurred during 2008-FY. This decrease was driven by the reduction in the weighted
average exercise price of the options outstanding during the period.
Interest Income
During 2009-FY the Company earned interest income of $48,000 compared to $293,000 for 2008FY. Interest income earned during a particular period is a function of investment products,
interest rate and / or investment yields available when funds become available for reinvestment as
well as average cash balances invested. Consequently, interest income and investment returns
have declined as a result of lower balances available to earn investment income, and a sharp
decline in returns available in the market.
Foreign Exchange Gain
For 2009-FY, the Company recorded a foreign exchange gain of $50,000 compared to a loss of
$171,000 during the 2008-FY period. This reflects the more stable currency markets in 2009,
particularly the Canadian versus US dollar, and the Company’s efforts to match foreign currency
expenditures and deposits.
RESULTS OF OPERATIONS
Three months ended December 31, 2009 compared to the three months ended December 31,
2008:
Summary of quarterly results for the eight quarters to December 31, 2009 (unaudited, in
thousands, except per share data):
Three months
ended:
Interest income
Total expenses
Net loss
December 31
2009
$
1
1,719
(1,717)
September 30
2009
$
3
2,211
(2,150)
June 30
2009
$ 10
1,814
(1,812)
March 31
2009
$
32
2,296
(2,263)
(0.03)
March 31
2008
$
87
2,132
(2,044)
Loss per share
Three months
ended:
Interest income
Total expenses
Net loss
(0.02)
December 31
2008
$
63
2,555
(2,491)
(0.03)
September 30
2008
$
90
2,587
(2,496)
(0.02)
June 30
2008
$ 50
1,936
(1,886)
Loss per share
(0.03)
(0.03)
(0.03)
(0.03)
The Company reported a net and comprehensive loss of $1.7 million or $0.02 per share in three
months ended December 31, 2009 (“2009-Q4”) compared to $2.5 million or $0.03 per share for the
three months ended December 31, 2008 (“2008-Q4”) - a drop of $774,000 and a drop of $433,000
over the previous quarter. The reduction from the comparative period in 2008 is a result of the
12
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
Company’s focus on the core BPH program as well as non-recurring clinical drug supply costs
incurred in 2008-Q4 with respect to the then planned PRX321 study of GBM.
Research and Development Costs
Research and development costs for the quarter ended December 31, 2009 dropped from the
comparative quarter in 2008 by $447,000 to $1.2 million reflecting the maturing effects of the
consolidation of our research and development programs to focus on the lead BPH program. We
exited the quarter with one active clinical program – our BPH TRIUMPH study – compared to
three active programs in the last quarter of 2008.
General and Administrative Costs
General and administrative costs were $206,000 lower in 2009-Q4 as compared to 2008-Q4 as the
cost reduction programs introduced early in 2009 matured.
Stock Based Compensation
Stock based compensation costs of $81,000 for the quarter ended December 31, 2009 increased by
$27,000 from the comparative quarter in 2008. This increase is due to the issuance of 2.4 million
options in the latter half of 2009.
Interest Income
The Company did not earn any material interest income in the last quarter of 2009, compared to
$64,000 in the comparative quarter in 2008 due to lower available market returns and lower balances
available to earn investment income.
Foreign Exchange Gain
The Company recorded a foreign exchange gain of $51,000 in the quarter ended December 31,
2009 compared to a loss of $153,000 during the last quarter of 2008. The loss in 2008-Q4 was
due to the sharp decline in the Canadian dollar in the last quarter of 2008, where as the Canadian
dollar increased modestly in value in the last quarter of 2009.
LIQUIDITY AND CAPITAL RESOURCES
Since inception, the Company has devoted its resources to funding R&D programs, including
discovery research, preclinical studies and clinical trial activities which has resulted in an
accumulated deficit of $38.3 million as of December 31, 2009. With current revenues consisting
only of interest earned on excess cash, losses are expected to continue while the Company’s
clinical programs are progressed.
At December 31, 2009, the Company had cash and cash equivalents of $1.8 million, representing
a net decrease of $4.9 million from December 31, 2008. The Company had working capital of
$818,000 at December 31, 2009, a decrease of $5.4 million from December 31, 2008.
The Company utilized cash resources of $7.5 million during 2009 to fund continuing operations,
a decrease of $1.1 million from the previous year. The Company’s average monthly consumption
13
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
of cash for operating and investing activities during 2009-FY was $575,000 compared to
$767,000 during 2008-FY.
On March 16, 2010, the Company closed a brokered private placement raising net proceeds of
$4.8 million from the issuance of 11.3 million units, with each unit comprised of one common
share of Protox and one-half of a common share purchase warrant. Each whole warrant entitles
the holder to purchase one common share of Protox at a price of $0.65 for a five year period from
closing date subject to an acceleration of the expiry date in certain circumstances. The additional
cash resources from the successful private placement will enable the company to continue its
research and development program.
Since early 2009, the Company has undertaken a comprehensive review of current development
and discovery programs, operations and anticipated expenditures with the view to reduce or defer
costs where possible in order to maximize available funds for priority initiatives. Management
believes that current cash resources should enable the Company to execute its core business plan
and meet its projected cash requirements into Q2-2011. The Company’s working capital may not
be sufficient to meet its stated business objectives in the event unforeseen circumstances or a
change in the strategic direction of the Company. When, or if, the Company requires additional
capital, there can be no assurance that the Company will be able to obtain further financing on
favorable terms, if at all.
As required, the Company will continue to finance its operations through the sale of equity or
pursue non-dilutive funding sources available to the Company in the future. Additional funding
could also be provided from collaborative arrangements established in the future with
pharmaceutical or biotechnology companies in relation to products and technologies under
development by the Company.
CONTRACTUAL OBLIGATIONS
Lease arrangements
The Company has entered into long-term operating lease arrangements for the rental of office and
laboratory facilities until April 2011amounting to total commitments of $108,000.
Clinical development programs
In connection with its clinical development programs, the Company has entered into a number of
contracts in the normal course of business that will remain in effect during 2010. These
commitments are performance based with payment subject to the achievement of clinical trial
milestones and generally may be cancelled with written notice. Total commitments amount to
$532,000.
PRX302 License Agreement for Prostate Cancer
Pursuant to an exclusive license agreement with John Hopkins University and the University of
Victoria, the Company has agreed to make cumulative milestone payments over the lifecycle of
PRX302 of up to $2.9 million contingent upon the achievement of certain clinical and regulatory
milestones and to pay royalties on commercial sales of resulting products. To December 31,
2009, the Company has paid milestone payments of $103,000.
14
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
PRX302 License Agreement for benign prostate hyperplasia
During 2009, the Company entered an exclusive license agreement with John Hopkins University
and the University of Victoria with respect to the use of PRX302 for the treatment of benign
prostate hyperplasia and other non-cancer diseases and conditions of the prostate. Pursuant to the
terms of this agreement, the company paid an upfront licensing fee of $45,000. The License
agreement requires the company to make payments of $1.2 million on the achievement of certain
clinical and regulatory milestones and to pay royalties on commercial sales of resulting products.
To December 31, 2009, the Company has paid milestone payments of $125,000.
INxin Technology License Agreement
Pursuant to an exclusive license agreement with the U.S. Public Health Service (“PHS”), the
Company has agreed to make cumulative milestone payments of up to US$4.0 million contingent
upon the achievement of certain clinical and regulatory milestones (for at least three indications)
and to pay royalties on commercial sales of resulting products.
HUMxin Technology License Agreement
Pursuant to an exclusive license agreement with PHS, the Company has agreed to make
cumulative milestone payments of up to US$4.8 million contingent upon the achievement of
certain clinical and regulatory milestones (for at least three indications) and to pay royalties on
commercial sales of resulting products.
Cooperative research and development agreements
The Company is party to two multi-year Collaborative Research and Development Agreements
(“CRADAs”) relating to its INxin and HUMxin technology with aggregate commitments of
US$800,000 over the term of the two CRADAs. As of December 31, 2009, the company has
future annual commitments remaining of US$125,000 per year until 2012.
TRANSACTIONS WITH RELATED PARTIES
During the year ended December 31, 2009, certain directors provided business advisory and
scientific consulting services to the Company pursuant to consulting agreements. The Company
incurred expenses of $94,000 (2008 - $132,000) under such agreements. These transactions were
incurred in the normal course of business and recorded at their exchange amounts.
CHANGES IN ACCOUNTING POLICIES
Goodwill and Intangible Assets
On January 1, 2009, the Company prospectively adopted CICA Handbook Section 3064 Goodwill
and Intangible Assets (“Section 3064”). This new accounting standard replaces Section 3062
Goodwill and Other Intangible Assets and Section 3450 Research and Development Costs. This
new accounting standard provides guidance on the recognition of intangible assets in accordance
with the definition of an asset and the criteria for asset recognition as well as clarifying the
application of the concept of matching revenues and expenses, whether these assets are separately
acquired or internally developed. The adoption of this new section did not have a significant
impact on the Company’s financial statements.
15
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
Credit Risk
In January 2009, the CICA issued Emerging Issues Committee (“EIC”) Abstract 173 - Credit
Risk and the Fair Value of Financial Assets and Financial Liabilities (“EIC-173”). EIC-173
provides guidance on how to take into account credit risk of an entity and counterparty when
determining the fair value of financial assets and financial liabilities, including derivative
instruments. EIC-173 is applicable for the Company’s interim and annual financial statements for
its fiscal year ending December 31, 2009, with retroactive application. The adoption of EIC-173
did not result in a material impact on the Company’s consolidated financial statements.
Financial Instruments Disclosure
The Company has adopted amendments to CICA Handbook Section 3862 Financial Instruments
– Disclosures, effective December 31, 2009. The disclosure requirements as a result of these
amendments are greater than previously required. The new disclosures require an entity to
classify fair value measurements using a fair value hierarchy that reflects the significance of the
inputs used in making the measurements. The fair value hierarchy shall have the following levels:
(a) quoted prices (unadjusted) in active markets for identical assets or liabilities (Level 1); (b)
inputs other than quoted prices included in Level 1 that are observable for the asset or liability,
either directly (i.e., as prices) or indirectly (i.e., derived from prices) (Level 2); and (c) inputs for
the asset or liability that are not based on observable market data (unobservable inputs) (Level 3).
CRITICAL ACCOUNTING POLICIES AND ESTIMATES
Use of estimates
The preparation of financial statements in conformity with Canadian GAAP requires management
to make estimates and assumptions that affect the reported amounts of assets and liabilities and
disclosure of contingent assets and liabilities at the dates of the financial statements and the
reported amounts of revenues and expenses during the reporting periods. Actual results could
significantly differ from those estimates.
Intangible assets
Intangible assets include proprietary rights, intellectual property, patent rights and technology
rights which have been acquired from third parties. Intangible assets are recorded at cost less
accumulated amortization. Following acquisition, the Company evaluates the prospective
commercialization of the acquired intangible asset. Depending upon the results of the evaluation,
the Company commences amortization of the assets over their expected useful lives, which is
generally less than ten years.
Long-lived assets
Long-lived assets are amortized over the estimated useful life of the asset and evaluated
periodically for impairment in accordance with Section 3063 Impairment of Long-lived Assets
(“Section 3063”). Section 3063 requires that long-lived assets, excluding goodwill and assets with
infinite useful lives, be evaluated for impairment when events or changes in facts and
circumstances indicate that their carrying value may not be recoverable. Events or changes in
facts or circumstances include but are not restricted to: a strategic change in business direction;
significant decrease in stock price; discontinuance of a product line or development program; or a
restructuring. If one of these events or circumstances indicates that the carrying value of an asset
may not be recoverable, or that our estimated amortization period was not appropriate, we would
16
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
record an impairment charge against of our long-lived assets. The amount of impairment would
be measured as the difference between the carrying value and the fair value of the impaired asset
as calculated using a net realizable value methodology. An impairment charge would be recorded
as an operating expense in the period of the impairment and as a reduction in carrying value.
Given the continued uncertainty capital markets, an impairment test was carried on definite lived
intangible assets at the end of 2009. Based on the assessment, no long-lived assets impairment
provision has been recorded to date. However, given the continued economic and capital markets
challenges, asset recoverability tests will continue to be performed in future periods.
Research and development costs
R&D costs are charged as an expense in the period in which they are incurred. Development costs
are charged as an expense in the period in which they are incurred unless they meet generally
accepted criteria under Canadian GAAP for deferral and amortization. No development costs
have been capitalized to date.
Patent costs
The costs incurred in establishing and maintaining patents for intellectual property developed are
expensed in the period incurred.
Stock-based compensation
The Company grants discretionary stock options for the purchase of common shares.
The Company accounts for all stock-based payments to employees and non-employees using the
fair value based method. Under the fair value based method, stock-based payments to employees
and non-employees are measured at the fair value of the equity instruments issued. The fair value
of stock-based payments to non-employees is periodically re-measured until the services are
provided or the options vest, and any change therein is recognized over the period.
ACCOUNTING PRONOUCEMENTS FOR FUTURE ADOPTION
International Financial Reporting Standards
In February 2008, the Accounting Standards Board of Canada confirmed that Canadian GAAP
for publicly accountable enterprises will be converged with International Financial Reporting
Standards (“IFRS”) effective for fiscal years beginning on or after January 1, 2011. The Company
will therefore be required to report using IFRS commencing with its unaudited interim
consolidated financial statements for the three months ended March 31, 2011, which must include
the interim results for the three months ended March 31, 2010 prepared on the same basis. IFRS
uses a conceptual framework similar to Canadian GAAP, but there are some significant
differences on recognition, measurement and disclosures.
Implementing IFRS will have a limited impact on accounting, financial reporting and supporting
IT systems and processes. It may also have an impact on actual commitments involving GAAP
based clauses, long-term employee compensation plans and performance metrics. Accordingly,
the Company is in the process of developing its IFRS changeover plan which will include
considerations such as measures to provide extensive training to key finance personnel, to review
contracts and agreements and to increase the level of awareness and knowledge amongst
17
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
management, the Board of Directors and the Audit Committee. Additional resources may be
engaged to ensure the timely conversion to IFRS.
The Company has completed a diagnostic between Canadian GAAP and IFRS. While the effects
of IFRS have not yet been fully determined, the Company has identified a number of areas where
it is likely to be impacted by changes in accounting policy. These include:
•
•
•
•
•
•
•
Property and equipment
Intangible assets
Impairment of assets
Provisions and contingent liabilities
Share-based payments
Related party disclosure
Presentation of statement of cash flows
As a first time adopter of IFRS, the Company is required to apply IFRS 1 “First time adoption of
International Financial Reporting Standards”. A number of exemptions are available under this
Standard which the Company is currently evaluating including electing to use fair value at the
transition date as deemed cost for capital assets in certain circumstances.
The implementation of IFRS is not expected to result in a material change to the financial
statements.
RISKS AND UNCERTAINTIES
The Company is subject to risks, events and uncertainties, or “risk factors”, associated with being
in the biopharmaceutical industry, and being an enterprise with projects in the research and
development stage. Such risk factors could cause reported financial information to not necessarily
be indicative of future operating results or of future financial position. The Company cannot
predict all of the risk factors, nor can it assess the impact, if any, of such risk factors on the
Company’s business or the extent to which any factor, or combination of factors, may cause
future results or financial position to differ materially from either those reported or those
projected in any forward-looking statements. Accordingly, historical financial information and
forward-looking statements should not be relied upon as a prediction of future results.
The Company is at an early stage of development and has incurred losses and will continue to
incur losses in the foreseeable future. Developing new technologies will require further
significant time and expense. It may be a number of years before the Company's technology
begins to generate revenues, if at all. There can be no assurance that any of the Company’s
developments will be successful or successful enough to be commercially viable. The Company
will need to raise additional funds to continue research and development and clinical trials
necessary for market approval. The Company cannot guarantee that financing will be available or
that terms for additional financing will be favourable.
As previously described, the Company expects cash and cash equivalents on hand will be
sufficient to fund operations into the second quarter of 2011. Funding requirements may vary
depending on a number of factors including progress in research and development, the cost
associated with conducting clinical trials and the regulatory approval process and the costs of
enforcing and prosecuting patent claims and other intellectual property rights.
18
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
The Company’s primary market risk is the exposure to foreign currency exchange rate
fluctuations. This risk arises from the Company’s holdings of foreign currency denominated
cash, accounts payable, cash equivalents, and short-term investments. Changes in foreign
currency exchange rates can create significant foreign exchange gains or losses to the Company.
The Company’s current foreign currency risk is primarily with the U.S. dollar. The Company has
minimal exposure to interest rate risks as it does not have long-term financial liabilities.
Additional information with respect to these and other risks affecting the Company is described in
the section “Risk factors” in the Company’s Annual Information Form dated March 29, 2010.
Reference should be made to the notes to the financial statements for the year ended December
31, 2009 and to the Company’s other continuous disclosure materials filed from time to time with
Canadian securities regulatory authorities, which are available online at www.sedar.com.
DISCLOSURE CONTROLS AND PROCEDURES
The Company maintains a set of disclosure controls and procedures designed to ensure that
information required to be disclosed in filings is recorded, processed, summarized and reported
within the time periods specified in the Canadian Securities Administrators’ rules and forms. Our
Chief Executive Officer (“CEO”) and Chief Financial Officer (“CFO”) have designed our
disclosure controls and procedures, or caused them to be designed under their supervision, as of
December 31, 2009, to provide reasonable assurance that material information relating to the
Company was made known to them and reported as required. The CEO and CFO have evaluated
the effectiveness of the Company’s disclosure controls and procedures as of December 31, 2009
and concluded that they provide reasonable assurance that material information relating to the
Company was made known to them and reported as required.
INTERNAL CONTROL OVER FINANCIAL REPORTING
Our CEO and CFO are responsible for the design of internal controls over financial reporting, or
for causing them to be designed under their supervision and, as of December 31, 2009, for
evaluating the effectiveness of such internal controls, to provide reasonable assurance regarding
the reliability of financial reporting and the preparation and fair presentation of external financial
statements in accordance with Canadian GAAP. Regardless of how well an internal control
system is designed and operated, it can provide only reasonable, not absolute, assurance that it
will prevent or detect all misstatements resulting from error or fraud due to the inherent
limitations of any internal control system. The CEO and CFO evaluated the design and
effectiveness of the Company’s internal controls over financial reporting based on the framework
established in Internal Control – Integrated Framework issued by the Committee of Sponsoring
Organizations of the Treadway Commission (COSO) and concluded that the Company’s internal
control over financial reporting was effective as of December 31, 2009. There were no changes
that occurred during the year ended December 31, 2009 that have materially affected, or are
reasonably likely to materially affect, the Company’s internal controls over financial reporting.
OTHER MD&A REQUIREMENTS
Outstanding Share Data
On March 16, 2010, the Company issued 11.3 million units under the terms of a brokered private
placement, with each unit comprised of one common share of Protox and one-half of a common
19
PROTOX THERAPEUTICS INC.
MANAGEMENT’S DISCUSSION AND ANALYSIS
December 31, 2009
share purchase warrant. Each whole warrant entitles the holder to purchase one common share of
Protox at a price of $0.65 for a five year period from closing date subject to an acceleration of the
expiry date in certain circumstances.
As at the date of this report, the Company has 96,037,698 common shares issued and outstanding.
In addition, the Company has 6,647,500 options outstanding to purchase common shares of the
Company. Of the options currently outstanding, approximately 3.9 million are exercisable into an
equivalent number of common shares of the Company at exercise prices ranging from $0.50 to
$1.00 and with an average exercise price of $0.69.
The Company also has 7,151,073 common share purchase warrants outstanding which expire
between May 2010 and March 2015 and entitle warrant holders to purchase common shares at a
prices ranging between $0.27 and $0.71. The weighted average warrant price is $0.60 and the
weighted average remaining term is 4.1 years. Furthermore, 6,367,269 of these common share
purchase warrants are subject to an acceleration of the expiry date if the closing price of the
underlying Common Shares is higher than $1.75 per common share for a period of 10 consecutive
trading days.
For a detailed summary of the outstanding securities convertible into, exercisable or exchangeable
for voting or equity securities as at December 31, 2009, refer to Note 8(b) and (d) in the audited
2009 annual financial statements of the Company.
20